Explaining the decision at the time, NICE's CEO said, "We
need to be
sure that new treatments provide sufficient benefits to patients to
justify the significant cost the NHS is being asked to pay. [Zelboraf] is an
expensive drug and its long-term benefits are difficult to quantify."

Last December, Novartis faced a similar
issue when NICE
rejected reimbursement for its multiple sclerosis treatment Gilenya. Again,
Dillon argued, "While Novartis submitted evidence that shows Gilenya can reduce
relapses, our independent
committee has not been convinced that it is a
cost-effective treatment option, even with the proposed Patient Access Scheme."

In both cases, of course, the companies argued that NICE was
wrong in their interpretations of the impact of these drugs on
patient
populations.

Fine, NICE isn't very nice when it comes to getting
expensive drugs to market in the U.K. Nothing new under the sun.
Similar pressures
are felt by drug companies in countries throughout Europe and in Canada, and
they are increasingly feeling the pressure from payors
within the United
States.

So why do I bring this up now?

Because, as I
begin research for two upcoming feature
articles on personalized medicine (which will appear in our October and
November issues), I realize that the
current challenges to convince payors to …
well, pay, will likely escalate as pharmaceutical firms develop a wider array
of drugs designed to more
effectively and safely treat smaller and smaller
patient communities.

The math speaks for itself. If the
cost of developing the
drug doesn't change (or at least not appreciably), but it is being delivered to
fewer patients, then the cost of treatment per
patient will need to be higher
to recoup the investment. This is something payors aren't happy to hear as they
face tightening budgets and expanding
patient rolls.

And Zelboraf is something of a poster-boy for this
challenge.

Touted by some as the prime
example of personalized medicine
at work, Zelboraf is targeted at a specific subset of metastatic melanoma
patients who share a common genetic profile
(positive for the V600E mutation of
B-Raf), and was co-developed with a diagnostic test (also from Roche) to
identify patients with this biomarker.

Despite its clear efficacy in clinical trials, however, NICE
expressed concern over the uncertainty of long-term survival benefits as many
patients in the trial switched treatment as their disease progressed, something
that happens commonly in cancer trials when one arm is shown to be
particularly
effective.

In this case, it seems that Roche did everything that has
been asked of them in the
co-development of a targeted therapy with a
diagnostic test to ensure only those patients most likely to benefit would
receive treatment, and yet they
are left scratching their heads, while patients
are left with what some might now consider suboptimal treatment options.

And this discussion is being held over treatment of patients
with a marker that occurs in a large percentage of the metastatic melanoma
population. What does the future hold for Vertex Pharmaceuticals
' Kalydeco,
approved in January as a treatment for a rare form of cystic fibrosis (carrying
the G551D mutation) that occurs in only 4 percent of CF
patients (about 1200
patients)?

Where companies traditionally have had to jump through hoops
to impress
regulators to approve the drugs they develop, they will increasingly
find themselves jumping through even narrower hoops to convince payors that
they
have made significant strides in improving patient care.

From a business perspective, that will mean paying even
closer attention to identifying the drug targets most likely to produce not
just safe and effective treatments, but safe and cost-effective treatments.
It
will mean rethinking the clinical trial process to ensure that the numbers look
as good as possible—not just better—when compared to current
standards of care,
which will rely on finding those patient subpopulations as early as possible.
And it may even mean repeating clinical trials once a
select patient population
has been identified as achieving a particularly outstanding benefit.

Ironically, we may
inadvertently increase the costs of drug
development while trying to ensure cost-effectiveness of the drugs that finally
make it to patients. For the
sake of payors, I hope the money they save today
by refusing payment will help offset some of the potential excesses later.

And for the pharmaceutical companies, the lesson might be:
If you build it, they will come … but they won't necessarily pay
for it, so
build wisely.

Willis is the features editor of ddn. He has worked at both
ends of the pharmaceutical industry, from basic research to marketing, and has
written about biomedical science for almost two decades.

EDITOR'S NOTE: We have recently been informed that
the NICE guidance
regarding Zelboraf was not a final guidance, but rather
a first-draft decision. The final guidance is not expected to be
published before December, according to NICE. Similarly, the
Gilenya discussion was centered on a first-draft decision, and in its
final
guidance, NICE recommended Gilenya for use by the NHS. We
regret any confusion we may have caused, and thank officials at NICE for
the
clarification.